27018-21-9

Usage

InChI:InChI=1/C9H10N4O/c1-14-6-4-2-3-5-7(6)8(10)13-9(11)12-5/h2-4H,1H3,(H4,10,11,12,13)

Upstream product

• 124-46-9 guanidine hydrogen carbonate 
• 94088-46-7 2-fluoro-6-methoxybenzonitrile 
• 1591-37-3 2-amino-6-methoxybenzonitrile 
• 29671-92-9 chloroformamidine hydrochloride 
• 1897-52-5 2,6 difluorobenzonitrile 
• 593-85-1 diguanidine carbonate 
• 593-85-1 guanidine carbonate 
• 67-56-1 methanol 
• 113-00-8 guanidine nitrate 

Relevant academic research and scientific papers

SNAr reaction in aqueous medium in the presence of mixed organic and inorganic bases

N-Arylation of amines with fluorobenzonitriles in aqueous medium is described. A mixture of N,N-diisopropylethyl amine and Na2CO3 (1:1) is found to achieve maximum conversion by refluxing for 3 hours in water. The product can be easily isolated by solvent extraction.

USE OF A QUINAZOLINE COMPOUND IN PREPARING A MEDICAMENT AGAINST FLAVIVIRIDAE VIRUS

Disclosed is a use of a quinazoline compound of Formula I having 2,4-diaminoquinazoline as a parent nucleus in preparation of a medicament for treating diseases caused by flaviviridae infection, especially a use in combating Hepatitis C virus infection and Dengue fever virus infection.

USE OF QUINAZOLINE COMPOUND IN PREPARATION OF ANTI-FLAVIVIRUS DRUG

Disclosed is a use of a quinazoline compound of Formula I having 2,4-diaminoquinazoline as a parent nucleus in preparation of a medicament for treating diseases caused by flaviviridae infection, especially a use in combating Hepatitis C virus infection an

Discovery and optimization of 2,4-diaminoquinazoline derivatives as a new class of potent dengue virus inhibitors

The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC50 = 0.15 μM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC50 = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile.

Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives as SMN2 promoter activators for the potential treatment of spinal muscular atrophy

Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord that is caused by deletion and/or mutation of the survival motor neuron gene (SMN1). Adjacent to SMN1 are a variable number of copies of the SMN2 gene. The two genes essentially differ by a single nucleotide, which causes the majority of the RNA transcripts from SMN2 to lack exon 7. Although both SMN1 and SMN2 encode the same Smn protein amino acid sequence, the loss of SMN1 and incorrect splicing of SMN2 have the consequence that Smn protein levels are insufficient for the survival of motor neurons. The therapeutic goal of our medicinal chemistry effort was to identify small-molecule activators of the SMN2 promoter that, by up-regulating gene transcription, would produce greater quantities of full-length Smn protein. Our initial medicinal chemistry effort explored a series of C5 substituted benzyl ether based 2,4-diaminoquinazoline derivatives that were found to be potent activators of the SMN2 promoter; however, inhibition of DHFR was shown to be an off-target activity that was linked to ATP depletion. We used a structure-guided approach to overcome DHFR inhibition while retaining SMN2 promoter activation. A lead compound 11a was identified as having high potency (EC50 = 4 nM) and 2.3-fold induction of the SMN2 promoter. Compound 11a possessed desirable pharmaceutical properties, including excellent brain exposure and long brain half-life following oral dosing to mice. The piperidine compound 11a up-regulated expression of the mouse SMN gene in NSC-34 cells, a mouse motor neuron hybrid cell line. In type 1 SMA patient fibroblasts, compound 11a induced Smn in a dose-dependent manner when analyzed by immunoblotting and increased the number of intranuclear particles called gems. The compound restored gems numbers in type I SMA patient fibroblasts to levels near unaffected genetic carriers of SMA.

Dicyclic and tricyclic diaminopyrimidine derivatives as potent inhibitors of Cryptosporidium parvum dihydrofolate reductase: Structure-activity and structure-selectivity correlations

A structurally diverse library of 93 lipophilic di- and tricyclic diaminopyrimidine derivatives was tested for the ability to inhibit recombinant dihydrofolate reductase (DHFR) cloned from human and bovine isolates of Cryptosporidium parvum (J. R. Vasquez et al., Mol. Biochem. Parasitol. 79:153-165, 1996). In parallel, the library was also tested against human DHFR and, for comparison, the enzyme from Escherichia coli. Fifty percent inhibitory concentrations (IC50s) were determined by means of a standard spectrophotometric assay of DHFR activity with dihydrofolate and NADPH as the cosubstrates. Of the compounds tested, 25 had IC50s in the 1 to l0 μM range against one or both C. parvum enzymes and thus were not substantially different from trimethoprim (IC50s, ca. 4 μM). Another 25 compounds had IC50s of 50s of 50s, 50s of 50s of 0.3 μM and thus were comparable in potency to trimetrexate. The finding that submicromolar concentrations of several of the compounds in the library could inhibit in vitro growth of C. parvum in host cells in the presence of thymidine (dThd) and hypoxanthine (Hx) suggests that lipophilic DHFR inhibitors, in combination with leucovorin, may find use in the treatment of intractable C. parvum infections.

Methods of modulating serine/thereonine protein kinase function with quinazoline-based compounds

The present invention is directed in part towards methods of modulating the function of serine/threonine protein kinases with quinazoline-based compounds. The methods incorporate cells that express a serine/threonine protein kinase, such as RAF. In additi

Direct Synthesis of 2,4-Diaminoquinazolines from 2-Fluorobenzonitriles

In a search for new methods for preparing 2,4-diaminoquinazolines having a diversity of substituents in the benzenoid ring, it was found that the reaction of 2,6-difluorbenzonitrile with guanidine carbonate gave 2,4-diamino-5-fluoroquinazoline in excellent yield.Extension of this approach to other 2-fluorobenzonitriles, some of which were elaborated for the first time, showed that this reaction possesses considerable generality.The cyclization was sucessful even when electron donating groups were present at position six.Only in two cases where a primary or secondary amino group was also present ortho to the cyano group was this transformation unsucessful.